TABLE 2

Comparison of the estimated PEG exposures in humans resulting from PEGylated protein or as an excipient in intravenous medicines

Other intravenous products and PEGylated proteins are available, but insufficient data could be found to allow estimation of exposure. These included Adagen (pegadamase bovine), Oncaspar (pegaspargase), and torsemide. Assumptions were: 1) data were estimated from product package inserts or labels (see www.fda.gov), 2) the highest dose presented in the insert was used in the estimate, and 3) specific gravity of PEG is 1.1 g/ml.


Compound

PEG Details

Estimated Body Burden

Comment
mg/week
μmol/week
Doses of PEG Associated with Acute Renal Failure in Patients
    Nitrofurantoin PEG300 121,000-220,000 400,000-750,000 6 of 32 patients (McCabe et al., 1959)
    Lorazepam PEG400 240,00 600,000 1 patient (Laine et al., 1995)
Intravenous Drugs Containing PEG as an Excipient
    Busulfex (busulfan) PEG400 110,000 275,000
    Vepesid (etoposide) PEG300 15,000 51,000
    Dipyridamole PEG600 400 670 Single injection
    Ativan (lorazepam) PEG400 200 500 Single injection
    Venoglobin-S (human globulin) Not stated, assumed PEG400 <28-280 <70-700 Blood product. PEG in preparation is an impurity. Based on acceptable purity limit
    Aralast (α1-proteinase inhibitor) Not stated, assumed PEG400 <0.6 <1.5 Blood product. PEG in preparation is an impurity. Based on acceptable purity limit
PEGylated Biological Products
    Somavert (pegvisomant) Multiple (4-5) 5-kDa PEG 200 40 PEGylated protein
    Neulasta (pegfilgrastim) Single 20-kDa monomethoxy PEG 6 0.3 PEGylated protein
    Pegasys (peginterferon α2a) 40-kDa branched bis methoxy PEG 0.18 0.005 PEGylated protein
    PEG-Intron (PEGylated interferon α2a)
Single 12-kDa monomethoxy PEG
0.11
0.006
PEGylated protein